Emerging evidence suggests that higher vitamin D blood levels are associated with better health outcomes including type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) but it remains unclear whether vitamin D supplementation could provide improvement of these health outcomes. A population of a priority interest to VA healthcare is a population of African American male (AAM) veterans at increased risk for T2DM. The goal of the proposed study is to determine the efficacy vitamin D treatment for improving early markers of T2DM, CVD and inflammation as compared to placebo in African American male (AAM) veterans at risk for T2DM. We will randomly assign AAM veterans with elevated plasma glucose (95-125 mg/dl) and low 25-hydroxyvitamin D (25OHD<20 ng/ml) to receive weekly vitamin D ergocalciferol 50,000 IU (D2) or placebo (PLA) for 12 months (90 subjects per group according to power analysis and assuming 15% drop out rate). At the baseline and at the end of the study we will perform clinical measurements (anthropometrics and blood bio-markers, HbA1c and lipid profile) and complete oral glucose tolerance test (OGTT) and frequently sampled intravenous glucose tolerance test (FSIVGTT). We will use Biorad BioPlex Multianalyte Profiler to simultaneously measure bio- markers of inflammation (interleukin-6 and tumor necrosis factor-alpha), of cardiovascular disease (sensitive C-reactive protein and plasminogen activator inhibitor-1), and adipokines (adiponectin and leptin). In addition we will measure fasting plasma glucose and HbA1c at 6 months. We will adjust D2 dose (while preserving double-blind design of the study) at 3 and 6 months to maintain 25OHD level in the sufficiency range of 40-100 ng/ml. The primary outcome will be change (post-treatment minus baseline) in oral glucose insulin sensitivity (OGIS) calculated from OGTT (Mari's formula). The key parameter calculated from FSIVGTT will be insulin sensitivity (SI, provides an estimate of insulin mediated glucose disposal based on Bergman's Minimal Model). We expect that at 12 months D2 will increase OGIS by about 10% and SI by 20%, and that these changes will be significantly better (p<0.05) than those seen in PLA. We also expect to see significant bio-markers'improvement of 10-25% in D2 compared to PLA group. We expect D2 to be well tolerated without significant adverse events. If the study shows positive outcomes it would suggest that vitamin D might be beneficial to enhance glucose metabolism by improving insulin-glucose interactions with a simple, weight- independent, and cost-effective intervention. Because lifestyle changes are difficult to achieve and maintain for preventing T2DM, D2 may be a possible option and should be considered for a trial of longer duration in a larger population to justify its use in the non-diabetic population. PUBLIC HEALTH RELEVANCE: The relevance of the proposed research to veterans'health Many veterans who have risk factors for type 2 diabetes also have vitamin D deficiency. Both conditions may lead to adverse health outcomes but produce no symptoms early on and may not be recognized by either patients or their physicians. This study will examine whether treatment of vitamin D deficiency in asymptomatic male veterans at risk for diabetes can provide health benefits. The study will use a generic form of vitamin D (available in VA pharmacies) that may provide simple and cost-effective way for VA healthcare to treat vitamin D deficient veterans if the study proves that vitamin D is beneficial.